59421145-Pathophysiology-of-Nerve-Injury.docx

Pathophysiology of nerve injury Physiology Anatomy 1. Schwann cells a. Myelinated and unmyelinated nerve axons b. Trophic factors (regenerative) c. Enclosed in basal membrane 2. Layers a. Endoneurium – supporting cells b. Perineurium – blood nerve barrier c. Epineurium – undulation (movement)

Axoplasmic transport 1. Cell bodies produce protein & transport to neurons 2. Fast (membrane bound) & Slow (soluble) transport – requires energy and Ca2+ 3. Antegrade (repair & synthesis) & Retrograde (recycling & breakdown) direction

Injury to peripheral nerves Neural (axons, Schwann cells, myelin) Regeneration – within 24h of injury More organized regeneration Restoration of function 2 main responses Axonal Segmental demyelination degeneration Slowing/ complete cessation of impulse condution

Response to injury Wallerian degeneration (Distal to injury)

Changes in myelinated fibres Axonal Myelin sheath, Schwann cell, macrophages Granular Partial collapse of myelin disintegration tube – 48h after injury (distal stump) Granular Production of myelin protein amorphous ↓ debris Remnants of Breakdown of myelin ↑ axon degeneration Myelin becomes segmented into ovoid Myelin removal by Schwann cells, hematogenous macrophages Schwann cell cytoplasm shrinks Ovoid segments ↓ in size Schwann cells undergo mitosis Tightly packed Schwann cells (distal stump) Changes in unmyelinated fibres Changes as in myelinated fibres Myelin degeneration not seen No prominent macrophage response Schwann cell proliferation occurs

Proximal end degeneratio n Similar to Wallerian degeneration Affects only up to 2 nodes of Ranvier (from point of injury)

Connective tissue (CT) Proliferation of CT cells haphazardly Repair by scar tissue Anatomical continuity (rather than restoration of function)

Cell body

End organs (muscle)

Chromatolysis (Nissl granules breakdown)  RNA become more active form  ↑ protein production  ↑ axonal transport

Muscle Atrophy Neighbouring uninjured nerve fibres may innervate muscle fibres that have lost nerve supply Change in muscle fibre characteristics Sarcolemma at N-M junction looses folds Nerve regeneration, recover normal structure Absense of innervations, muscle atrophy, irreversible fibrosis (2 years), motor end plate degenerate completely (18-24 months)

Cell body swell up Nucleus pushed to periphery Axonal stump (if lesion close to cell body) Death of cell body (no regeneration possible) (if injury severe)

Sensory Area shrinks due to recovery from neuropraxia (functional, not anatomical defect) Adjacent branches supply anaesthetic area

Classification of Injury Neuropraxia Axonotmesis Nerve conduction Anatomical interruption of axon with no/partial blocked (without interruption to CT (preservation of perineural anatomical continuity) interruption) Loss of neurological Fascicular alignment mostly preserved function is temporary Full recovery takes 2 extends of injury are possible place Local segmental Sunderland Grade 2 Sunderland Grade 3 Axon continuity is Disrupt axon, myelin, demyelination (most disrupted endoneurium severe) Myelin shealth continuity Large diameter may/may not be fibres (most preserved initially susceptible) Basement membrane is Chance to recovery ↓ No Wallerian preserved than Grade 2 degeneration Wallerian degeneration Continuity of basal Distal segment occurs 2° to axonal lamina is lost (likelihood retain nerve damage in distal of neuritis growing into conduction capacity Recovery in a few segment (lead to inappropriate distal days (rarely longer) breakdown of myelin) segments higher) Sunderland Grade Recovery is sequentially 1 injury from proximal to distal

Neurotmesis Complete anatomical disruption (axon, surrounding CT)

Sunderland Grade 4 Both axons, CT loose continuity Nerve not completely severed Interfascicular epineural CT, perineurium disrupted Fascicular continuity is lost (different from axonotmesis) Neurites caught in fibrous tissue scars May be in inappropriate fasciculus when they find distal stumps Endoneural proliferation, narrowing of distal stumps, fibre diameter will be smaller, function compromised

Sunderland Grade 5 Nerve severed completely Neuroma formation (if not repaired)

Neural regeneration 1. Reversal of chromatolysis 2. Axonal transport of materials 3. Axonal sprouting a. Prolonged denervation prevent regeneration of axons to enter appropriate tubes b. Failure to enter due to i. Scar formation ii. Too long gap

Factors influencing prognosis 1. Age – younger better 2. Site 3. Severity 4. Type 5. Tension 6. Sepsis 7. General factors – condition, nutrition of patient 8. Timing of repair – earier better

Nerve injury & Wallerian degeneration

Nerve regeneration

Tests of regeneration 1. Clinical a. Reassess motor, sensory, autonomic function b. Examinte scar tissue and neuroma c. Tinel’s sign 2. Electrophysiology a. Electromyography b. Nerve conduction studies